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    EPAC proteins are the guanine nucleotide exchange factors that act as the intracellular receptors for cyclic AMP. Two variants of EPAC genes including EPAC1 and EPAC2 are cloned and are widely expressed throughout the brain. But, their functions in the brain remain unknown. Here, we genetically delete EPAC1 (EPAC1(-/-)), EPAC2 (EPAC2(-/-)), or both EPAC1 and EPAC2 genes (EPAC(-/-)) in the forebrain of mice. We show that EPAC null mutation impairs long-term potentiation (LTP) and that this impairment is paralleled with the severe deficits in spatial learning and social interactions and is mediated in a direct manner by miR-124 transcription and Zif268 translation. Knockdown of miR-124 restores Zif268 and hence reverses all aspects of the EPAC(-/-) phenotypes, whereas expression of miR-124 or knockdown of Zif268 reproduces the effects of EPAC null mutation. Thus, EPAC proteins control miR-124 transcription in the brain for processing spatial learning and social interactions. Copyright © 2012 Elsevier Inc. All rights reserved.

    Citation

    Ying Yang, Xiaogang Shu, Dan Liu, You Shang, Yan Wu, Lei Pei, Xin Xu, Qing Tian, Jian Zhang, Kun Qian, Ya-Xian Wang, Ronald S Petralia, Weihong Tu, Ling-Qiang Zhu, Jian-Zhi Wang, Youming Lu. EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268 translation. Neuron. 2012 Feb 23;73(4):774-88

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    PMID: 22365550

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